Antidepressant Drugs Modulate Differentially Anti-inflammatory Lithium’s Property: An in Vitro and in Vivo Study

Li (lithium), a mood stabilizer has anti-inflammatory effect. However, in clinical practice, Li can be administered together with other antidepressants drugs, such as FLX (fluoxetine), IMI (imipramine), NOR (nortriptyline) and ESC (escitalopram). As interaction between Li and these antidepressant drugs on inflammatory modulation has not been investigated yet, we performed an in vitro protocol using a non-human macrophage cell line. Oxidative and inflammatory markers, as well as cell cycle analysis and cytokine gene expressions were compared among treatments. An IR (inflammatory ratio) was calculated based on the following oxidative-inflammatory variables: nitric oxide, superoxide anion, reactive oxygen molecules, cytokines IL-1β, IL-6, TNF-α and IL-10. The in vitro calculated IR data were validated through an in vivo analysis of 154 human subjects with similar IR. Li and control cells presented similar IR values. FLX, NOR and IMI increased slightly IR values indicating some proinflammatory effect, whereas ESC decreased IR values indicating some anti-inflammatory effect. However, cells exposed to Li + ESC triggered a proinflammatory response on macrophages. Thus, IR comparison results suggest that the Li anti-inflammatory effect is not universal and could be influenced by both basal macrophage-inflammatory state and interaction of other psychiatric drugs. These results could be useful tounderstand some inconsistencies observed in human studies involving Li and other psychiatric drugs.